SOX11调控骨髓间充质干细胞分化与迁移的研究及其在骨/软骨再生中的应用

Mesenchymal stem cells are an important cell source for tissue engineering, especially for bone and cartilage repair. However, the osteogenic and chondrogenic differentiation potential of MSCs in vivo are still rather limited, which hinders the application of MSC in tissue engineering. It is generally believed that the peripheral blood derived MSCs (PB-MSCs) are associated with stronger homing potential, and are from bone marrow. In our previous studies, we found that SOX11 was highly expressed in PB-MSCs through microarray analysis, as compared with bone marrow derived MSCs (BM-MSCs). It has been reported that silencing SOX11 by siRNA inhibited osteogenic, adipogenic differentiation as well as the stemness of MSC, but the underlying mechanisms are still unknown. Our preliminary results show that SOX11 overexpression promotes the tri-lineage differentiation and migration of MSCs. In this study, we aim to investigate the underlying mechanisms how SOX11 regulates the differentiation, migration and stemness of MSCs, to explore the application of SOX11 modified MSCs in bone and cartilage repair. Using microarray, dual luciferase report system and CHIP assays, we plan to investigate the mechanisms in MSCs overexpressing or koncking down SOX11. SD rats with open femur fracture or cartilage defect will be used to evaluate the effects of SOX11 modified MSCs for bone and cartilage tissue repair. This study will shed light on the role of SOX11 in MSCs-based cell therapy.

间充质干细胞（MSCs）是骨/软骨损伤修复中非常有前景的干细胞来源。但MSCs在体内分化为功能性的成骨细胞和软骨细胞的能力依然有限，严重阻碍了MSC在组织工程中的应用。一般认为外周血MSC来源于骨髓，具有更强的归巢潜能。我们通过基因芯片分析发现SOX11在外周血MSC中的表达量明显高于骨髓MSCs。我们的预实验结果进一步表明，SOX11在MSC的多向分化及迁移能力方面均发挥重要的调控作用。本研究的目的在于阐明SOX11调控MSC分化、迁移及细胞干性的相关机制，并探索过表达SOX11的MSC在骨折及软骨损伤修复模型中的应用。我们拟应用SOX11过表达及shRNA 干扰的MSC细胞模型及大鼠的开放性股骨骨折模型和软骨缺损模型，通过基因芯片、双荧光素酶报告系统、染色质免疫共沉淀、显微CT等技术，从基因-细胞-个体层次实现上述目标。此研究将为以MSCs为基础的干细胞治疗提供新的思路和靶点。

间充质干细胞（MSCs）是骨和软骨损伤修复中非常重要的种子细胞。但MSC在体内分化为功能性的成骨细胞或软骨细胞的能力依然有限，严重阻碍了MSC在组织工程中的应用。外周血MSC来源于骨髓，具有更强的归巢潜能。我们通过基因芯片分析发现SOX11在外周血MSC中的表达量明显高于骨髓MSC。本研究的目的在于（1）全面系统研究SOX11基因在MSC分化和迁移中所起的作用；（2）阐明SOX11调控MSC分化和迁移的分子机制；（3）进一步探索SOX11基因修饰的MSC在骨折和软骨损伤修复中的作用，以便为骨折和软骨损伤修复提供新的靶点。我们拟应用SOX11过表达及shRNA 干扰的MSC细胞模型及大鼠的开放性股骨骨折模型和软骨缺损模型，通过基因芯片、双荧光素酶报告系统、染色质免疫共沉淀、显微CT等技术，从基因-细胞-个体层次实现上述目标。此研究将为以MSC为基础的干细胞治疗提供新的思路和靶点。本课题于2014年1月按计划开题，以上三个目的科研计划均已按计划实施，并全部完成。